A transient modified mRNA encoding Myc and cyclin T1 improves cardiac function after myocardial injury
Abstract Myc is an evolutionarily conserved transcription factor that is necessary for the restoration of tissues in multiple regenerative species. The adult mammalian heart lacks regenerative capacity and cardiomyocytes fail to divide following damage-induced signaling. Transgenic expression of Myc and cyclin T1 can drive substantial adult cardiomyocyte proliferation to replace lost cardiomyocytes. Here, using transgenic models and a prototypical mRNA therapeutic, we show that Myc and cyclin T1 require transient induction for cardiomyocyte proliferation that leads to myocardial repair and functional recovery after myocardial infarction in mice. This research provides a strategy to translate Myc–cyclin T1 coexpression for cardiac regeneration to address serious unmet needs in the treatment of cardiovascular disease.
Authors
- Jasmin Straube (ORCID: https://orcid.org/0000-0002-1748-0659)
- Henrietta Cserné Szappanos (ORCID: https://orcid.org/0000-0003-0063-257X)
- Karin Jennbacken (ORCID: https://orcid.org/0000-0003-1254-5158)
- Mauro Giacca (ORCID: https://orcid.org/0000-0003-2927-7225)
- Brian Wan-Chi Tse (ORCID: https://orcid.org/0000-0002-5982-8369)
- Christopher R. Hunter (ORCID: https://orcid.org/0009-0003-1362-5085)
- James E. Hudson (ORCID: https://orcid.org/0000-0003-0832-9356)
- Sanjay Sinha (ORCID: https://orcid.org/0000-0001-5900-1209)
- Ana Vujić (ORCID: https://orcid.org/0000-0002-0559-5299)
- Enzo R. Porrello (ORCID: https://orcid.org/0000-0001-6105-7463)
- Megan J. Bywater (ORCID: https://orcid.org/0000-0002-7466-6927)
- Patrícia Gonçalves‐Rodrigues (ORCID: https://orcid.org/0000-0003-3767-2559)
- Christopher A. P. Batho (ORCID: https://orcid.org/0000-0002-4687-3101)
- Silvia Da Pra (ORCID: https://orcid.org/0000-0001-6906-2806)
- Kenny M. Hansson (ORCID: https://orcid.org/0000-0003-0448-5140)
- Gregory A. Quaife-Ryan (ORCID: https://orcid.org/0000-0002-0012-9934)
- Gabriele D’Uva (ORCID: https://orcid.org/0000-0001-9622-9288)
- Elsa Lawrence (ORCID: https://orcid.org/0000-0003-4280-0367)
- Gina Hyberg
- Catherine H. Wilson (ORCID: https://orcid.org/0000-0002-5333-0295)
- Camilla Ascanelli (ORCID: https://orcid.org/0000-0002-6266-2822)
- Aleksandra Boikova
- Kamil A. Sokolowski (ORCID: https://orcid.org/0000-0003-3679-2321)
- Harley Robinson (ORCID: https://orcid.org/0000-0002-9374-5532)
- Rowda Dahir (ORCID: https://orcid.org/0009-0005-0030-1182)
- Qing‐Dong Wang (ORCID: https://orcid.org/0000-0001-9570-4411)
- Adam Seaton
- Thomas Krieg (ORCID: https://orcid.org/0000-0002-5192-580X)
- Maria Victoria Rodriguez Noci
- Jin Seok Lee
- Kypros Kyprianou Kokonos
- Alby Biju
Institutions
- Translational Research Institute (AU)
- Royal Children's Hospital (AU)
- University of Trieste (IT)
- Queensland University of Technology (AU)
- The University of Queensland (AU)
- The University of Melbourne (AU)
- King's College London (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- QIMR Berghofer Medical Research Institute (AU)
- University of Cambridge (GB)
- The Gurdon Institute (GB)
- British Heart Foundation (GB)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Prince Charles Hospital (AU)
- AstraZeneca (Sweden) (SE)
- Murdoch Children's Research Institute (AU)
- Addenbrooke's Hospital (GB)
- University of Bologna (IT)
Publication Details
- Journal
- Nature Cardiovascular Research
- Published
- 2026-11-09
- DOI
- https://doi.org/10.1038/s44161-026-00910-7
- Citations
- 1
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 1.35